This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Abstract Using Molecular Dynamic (MD) simulations, computational protein modification, and Thermodynamic Integration (TI) method we will concentrate on the studying of the PDZ-ligand complexes of Na/H Exchange Regulatory Factor-1 (NHERF1) due to their biological and medicinal importance. We will investigate the PDZ2-ligand interactions. To probe such interactions we will use the five amino acid residue motifs WETVM (L1) or LFSNL (L2). We are planning to estimate binding affinity of PDZ2 for both L1 and L2.